Catabolism of the human erythrocyte C3b/C4b receptor (CR1, CD35): vesiculation and/or proteolysis?
Human erythrocytes (E) react by exocytosis of membrane vesicles to various stresses including the fixation of the membrane attack complex of Complement. E from normal individuals loose a notable proportion of their initial number of surface CR1 molecules during the ageing process. An acquired decrease of CR1 on E also occurs in pathological conditions such as Systemic Lupus Erythematosus or AIDS. The present study investigated whether calcium ionophore A23187 (Ca-ion) induced vesicle formation of human E in vitro is responsible for a preferential loss of CR1 as well as whether CR1 molecules at the surface of Ca-ion treated E or vesicles are: (i) functional, (ii) native or protease degraded, or (iii) more clustered than CR1 on native E. A study of E from 137 normal individuals showed that a one-hour Ca-ion induced vesicle formation preferentially removed one third of E surface CR1. Kinetic experiments suggested that all surface CR1 could be removed from E upon longer incubation times. CR1 molecules on vesicles were still able to inhibit Complement activation, and were found in larger clusters than on native E. These data suggest that a significant part of surface CR1 molecules may be removed from E by vesicle formation during the life of E in normal individuals. This phenomenon could be exacerbated in pathological conditions.
Dervillez
X
X
Laboratoire d'Immunologie, CHU Robert Debré, Reims, France.
Oudin
S
S
Libyh
M T
MT
Tabary
T
T
Reveil
B
B
Philbert
F
F
Bougy
F
F
Pluot
M
M
Cohen
J H
JH
D000375:Aging / Q000276:immunology; D000483:Alleles; D000001:Calcimycin / Q000494:pharmacology; D015923:Complement C1r / Q000235:genetics*; D015935:Complement C4b / Q000276:immunology; D003169:Complement Inactivator Proteins; D015938:Complement Membrane Attack Complex / Q000378:metabolism; D004912:Erythrocytes / Q000187:drug effects / Q000276:immunology*; D005089:Exocytosis / Q000187:drug effects* / Q000276:immunology; D005434:Flow Cytometry; D006023:Glycoproteins; D006801:Humans; D007150:Immunohistochemistry; D007476:Ionophores / Q000494:pharmacology; D008854:Microscopy, Electron; D010206:Papain / Q000494:pharmacology; D012150:Polymorphism, Restriction Fragment Length; D011951:Receptors, Complement / Q000187:drug effects*; D017463:Receptors, Complement 3b / Q000187:drug effects*; D013572:Synaptic Vesicles / Q000187:drug effects / Q000378:metabolism
D003169:Complement Inactivator Proteins; D015938:Complement Membrane Attack Complex; D006023:Glycoproteins; D007476:Ionophores; D011951:Receptors, Complement; D017463:Receptors, Complement 3b; D000001:Calcimycin; D015935:Complement C4b; D015923:Complement C1r; D010206:Papain